Letellier Kareen, Azeddine Bouziane, Blain Sacha, Turgeon Isabelle, Wang Da Shen, Boiro Mamadou Samba, Moldovan Florina, Labelle Hubert, Poitras Benoît, Rivard Charles-Hilaire, Grimard Guy, Parent Stefan, Ouellet Jean, Lacroix Ginette, Moreau Alain
Centre de recherche, CHU Sainte-Justine, Laboratoires de Génétique Moléculaire et de Biologie Cellulaire et Tissulaire des Maladies Musculo-Squelettiques, 3175, chemin de la Côte-Ste-Catherine, Montréal (Québec), H3T 1C5 Canada.
Med Sci (Paris). 2007 Nov;23(11):910-6. doi: 10.1051/medsci/20072311910.
Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis that affects a significant number of young teenagers, mainly females (0.2-6 % of the population). Historically, several hypothesis were postulated to explain the aetiology of AIS, including genetic factors, biochemical factors, mechanics, neurological, muscular factors and hormonal factors. The neuroendocrine hypothesis involving a melatonin deficiency as the source for AIS has generated great interest. This hypothesis stems from the fact that experimental pinealectomy in chicken, and more recently in rats maintained in a bipedal mode, produces a scoliosis. The biological relevance of melatonin in idiopathic scoliosis is controversial since no significant decrease in circulating melatonin level has been observed in a majority of studies. Analysis of melatonin signal transduction in musculoskeletal tissues of AIS patients demonstrated for the first time a defect occurring in a cell autonomous manner in different cell types isolated from AIS patients suffering of the most severe form of that disease. These results have led to a classification of AIS patients in three different functional groups depending on their response to melatonin, suggesting that the cause of AIS involves several genes. Molecular analysis showed that melatonin signaling dysfunction is triggered by an increased phosphorylation of Gi proteins inactivating their function. This discovery has led to development of a first scoliosis screening assay. This test, using blood sample, is currently in clinical validation process in Canada and could be used for screening children at high risk of developing AIS.
青少年特发性脊柱侧凸（AIS）是脊柱侧凸最常见的形式，影响大量青少年，主要是女性（占人口的0.2 - 6%）。历史上，人们提出了几种假说来解释AIS的病因，包括遗传因素、生化因素、力学因素、神经因素、肌肉因素和激素因素。涉及褪黑素缺乏是AIS病因的神经内分泌假说引起了极大关注。这一假说源于这样一个事实，即对鸡进行实验性松果体切除，以及最近对以双足模式饲养的大鼠进行松果体切除，都会导致脊柱侧凸。褪黑素在特发性脊柱侧凸中的生物学相关性存在争议，因为在大多数研究中未观察到循环褪黑素水平有显著下降。对AIS患者肌肉骨骼组织中褪黑素信号转导的分析首次证明，在从患有最严重形式该疾病的AIS患者分离出的不同细胞类型中，以细胞自主方式发生了缺陷。这些结果导致根据AIS患者对褪黑素的反应将其分为三个不同的功能组，这表明AIS的病因涉及多个基因。分子分析表明，褪黑素信号功能障碍是由Gi蛋白磷酸化增加使其功能失活引发的。这一发现促成了首个脊柱侧凸筛查检测方法的开发。该检测方法使用血样，目前正在加拿大进行临床验证，可用于筛查有发展为AIS高风险的儿童。
